2016年 · 第05卷第06期

Visceral leishmaniasis, commonly known as kala-azar in India, is a global public health problem. In Southeast Asia, Bangladesh, Bhutan, India, Nepal, Sri Lanka and Thailand are endemic for visceral leishmaniasis. The role of sandflies as the vector of kala-azar was first confirmed in 1942 in India. Insecticide resistance in Phlebotomus argentipes Annandale and Brunetti, the vector of kala-azar in the Indian subcontinent, was first reported in 1987 in Bihar, India. This article provides a scoping review of the studies undertaken from 1959 to 2015 on insecticide resistance in P. argentipes and P. papatasi (Scopoli), the vectors of visceral and cutaneous leishmaniasis respectively, in Southeast Asia, mainly in Bangladesh, India, Nepal and Sri Lanka.

Studies undertaken in areas of Bihar and West Bengal in India where kala-azar is endemic have reported resistance of P. argentipes to DDT, while in non-endemic areas it has been reported to be susceptible. In areas of Nepal bordering India, there are indications of resistance to DDT; biochemical resistance has been reported in Sri Lanka. No laboratory studies have been undertaken in Bangladesh; however, the sandfly vector is reported to be still susceptible to pyrethroids in all kala-azar endemic areas in the aforementioned countries.

Studies are needed to determine the resistance of sandfly vectors to all available classes of potential insecticides in kala-azar endemic areas. There is a need to assess the impact of indoor residual spraying with DDT and pyrethroids on the incidence of kala-azar in India where 54 districts remain endemic for the disease, strengthen entomological surveillance capacity, and develop and implement an insecticide management plan. Alpha-cypermethrin indoor residual spraying has been introduced in 33 kala-azar endemic districts in Bihar State of India in a pilot trial; the outcomes should be used to inform decisions on expanding coverage with alpha-cypermethrin in all remaining endemic districts to achieve the revised goal of elimination of visceral leishmaniasis by 2020.

Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.

To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners’ collaboration. However, no reviews were focused following various preclinical and clinical studies published since the MMV initiation (2000) to till date.

We identify promising approaches in the global portfolio of antimalarial medicines, and highlight challenges and patient specific concerns of these novel molecules. We discuss different clinical studies focusing on the evaluation of novel drugs against malaria in different human trials over the past five years.

The drugs KAE609 and DDD107498 are still being evaluated in Phase I trials and preclinical developmental studies. Both the safety and efficacy of novel compounds such as KAF156 and DSM265 need to be assessed further, especially for use in pregnant women. Synthetic non-artemisinin ozonides such as OZ277 raised concerns in terms of its insufficient efficacy against high parasitic loads. Aminoquinoline-based scaffolds such as ferroquine are promising but should be combined with good partner drugs for enhanced efficacy. AQ-13 induced electrocardiac events, which led to prolonged QTc intervals. Tafenoquine, the only new anti-relapse scaffold for patients with a glucose-6-phosphate dehydrogenase deficiency, has raised significant concerns due to its hemolytic activity. Other compounds, including methylene blue (potential transmission blocker) and fosmidomycin (DXP reductoisomerase inhibitor), are available but cannot be used in children.

At this stage, we are unable to identify a single magic bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

Intestinal schistosomiasis due to Schistosoma mansoni was first reported in Oman in 1979. We describe the trend in parasitological and serological prevalence of human infection with S. mansoni in the endemic area over the period 1982–2014, and the compliance of data generated by the national monitoring and evaluation system with schistosomiasis elimination criteria set by the Ministry of Health of Oman.

Parasitological and serological assessments were carried out on population (mainly children) living in the area at risk for schistosomiasis in Dhofar, the country’s only endemic Governorate, for a period of over 30 years. Kato-Katz thick smear and Indirect Haemagglutination Assay were the techniques employed.

Data indicate a progressive decline in prevalence of S. mansoni throughout the 1980s and the 1990s, a recrudescence in the early 2000s, and a more marked decrease following the implementation of six rounds of mass treatment with praziquantel from 2007 to 2013. Latest parasitological prevalence (2011) was 0%, while latest serological prevalence (2014) was 0.11%.

Transmission of schistosomiasis has reached very low levels in Oman. Elimination criteria established by the Ministry of Health of Oman (parasitological prevalence ≤ 1% and serological prevalence ≤ 5%) have been met since 2008. Further investigations are required to assess whether interruption of transmission has been achieved in some or all foci, in view of the establishment of a formal verification process under the auspices of WHO.

The predictive value of the serology to detection of IgM against the Mycobacterium leprae-derived phenolic glycolipid-I/PGL-I to identify leprosy patients who are at higher risk of developing reactions remains controversial. Whether baseline results of the ML Flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR).

This was a descriptive study focusing on the main clinical manifestations of leprosy patients enrolled in the U-MDT/CT-BR from March 2007 to February 2012 at two Brazilian leprosy reference centers. For research purposes, 753 leprosy patients were categorized according to a modified Ridley-Jopling (R&J) classification and according to the development of leprosy reactions (reversal reaction/RR and erythema nodosum leprosum/ENL), and whether they had a positive or negative bacillary index/BI.

More than half of the patients (55.5 %) reported leprosy reaction: 18.3 % (138/753) had a RR and 5.4 % (41/753) had ENL. Leprosy reactions were more frequent in the first year following diagnosis, as seen in 27 % (205/753) of patients, while 19 % (142/753) developed reactions during subsequent follow-up. Similar frequencies of leprosy reactions and other clinical manifestations were observed in paucibacillary (PB) and multibacillary (MB) leprosy patients treated with U-MDT and regular MDT (R-MDT) (P= 0.43 and P= 0.61, respectively). Compared with PB patients, leprosy reactions were significantly more frequent in MB patients with a high BI, and more patients developed RR than ENL. However, RR and neuritis were also reported in patients with a negative BI. At baseline, the highest rate of ML Flow positivity was observed in patients with a positive BI, especially those who developed ENL, followed by patients who had neuritis and RR. Among reaction-free patients, 81.9 % were ML Flow positive, however, the differences were not statistically significant compared to reactional patients (P= 0.45).

MB and PB patients treated with R-MDT and U-MDT showed similar frequencies of RR and other clinical manifestations. Positive ML Flow tests were associated with MB leprosy and BI positivity. However, ML Flow test results at baseline showed limited sensitivity and specificity for predicting the development of leprosy reactions.

Despite the availability of Anti-Retroviral Therapy (ART), the health-related quality of life (HRQoL) among HIV-positive men who have sex with men (HIVMSM) in China remains poor. This study aimed to explore the relationship between self-reported psychopathology and HRQoL among HIVMSM in Dalian, China.

A cross-sectional study was conducted in 112 HIVMSM. Symptom check list 90 (SCL 90): a measure of psychopathology and World Health Organization quality of life in HIV infection (WHOQOL-HIV-Bref): a measure of HRQoL were used. Correlation and multiple regression analysis were employed to explore the association between self-reported psychopathology and HRQoL in HIVMSM.

Out of the total 112 HIVMSM cases, 9 (8 %) cases were homosexuals and 103 (92 %) ones were bisexuals. The participants who had low family income (P= 0.001), perceived discrimination (P= 0.001) and lack of regular attendance in medical follow-ups (P= 0.014) reported poorer HRQoL than their counterparts. Somatization, obsession, depression, phobia and overall SCL 90 scores in self-reported psycholpathology had a negative impact on the domains of HRQoL among HIVMSM.

Total quality of life was predicted by family income, perceived discrimination, and medical follow-up attendance. Self-reported psychopathology was negatively correlated with HRQoL in HIVMSM. The Strategies that target MSM focusing on linking and engaging HIV-positive patients in medical care is the key step to improve their HRQoL. More emphasis is needed on the newly diagnosed HIVMSM in Dalian in order to develop a more targeted intervention to prevent perceived discrimination and lack of proper medical follow-up services.

The trial registration number does not require for this manuscript. The study is cross-sectional design that do not involve intervention at all, it is not a clinical trial.

Tuberculosis/HIV co-infection is a bidirectional and synergistic combination of two very important pathogens in public health. To date, there have been limited clinical data regarding mortality rates among tuberculosis/HIV co-infected patients and the impact of antiretroviral therapy on clinical outcomes in Ethiopia. This study assessed the incidence and predictors of tuberculosis/HIV co-infection mortality in Southwest Ethiopia.

A retrospective cohort study collated tuberculosis/HIV data from Jimma University Teaching Hospital for the period of September 2010 and August 2012. The data analysis used proportional hazards cox regression model at P value of ≤ 0.05 in the final model.

Fifty-five (20.2 %) patients died during the study period and 272 study participants contributed 3 082.7 person month observations. Factors including: being aged between 35–44 years (AHR = 2.9; 95 % CI: 1.08–7.6), being a female sex worker (AHR= 9.1; 95 % CI: 2.7–30.7), being bed ridden as functional status (AHR = 3.2; 95 % CI: 1.2–8.7), and being at World Health Organization HIV disease stages 2 (AHR = 0.2; 95 % CI: 0.06–0.5), 3(AHR = 0.3; 95 % CI: 0.1–0.8) and 4(AHR= 0.2; 95 % CI: 0.04–0.55) were significant predictors of mortality for tuberculosis/HIV co-infected patients.

Contrary to our expectations, the World Health Organization (WHO) HIV disease stage 1 was found to be a significant predictor of mortality. Higher mortality rates were observed in WHO disease stage 1 patients compared to patients in stages 2, 3 and 4. The current study also confirmed and reaffirmed known significant predictors of the mortality for tuberculosis/HIV co-infected patients including being 35–44 years, being a female sex worker and being bed ridden functional status. The occurrence of high death rate among tuberculosis/HIV co-infected cases needs actions to reduce this poor outcome.

Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak.

The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV).

Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10⁶ copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10⁶ copies/ml. Multivariate analyses showed that blood viral load (P= 0.005), confusion (P= 0.010), abdominal pain (P= 0.003), conjunctivitis (P= 0.035), and vomiting (P= 0.004) were factors independently associated with the outcomes of EVD patients.

Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients.

Despite recurring outbreaks of cholera in Ghana, very little has been reported on assessments of outbreak response activities undertaken in affected areas. This study assessed the response activities undertaken in two districts, Akatsi District in Volta Region and Komenda-Edina-Eguafo-Abirem (KEEA) Municipal in Central Region during the 2012 cholera epidemic in Ghana.

We conducted a retrospective assessment of the events, strengths and weaknesses of the cholera outbreak response activities in the two districts making use of the WHO cholera evaluation tool. Information sources included surveillance and facility records, reports and interviews with relevant health personnel involved in the outbreak response from both district health directorates and health facilities. We collected data on age, sex, area of residence, date of reporting to health facility of cholera cases, district population data and information on the outbreak response activities and performed descriptive analyses of the outbreak data by person, time and place.

The cholera outbreak in Akatsi was explosive with a high attack rate (AR) of 374/100,000 and case fatality rate (CFR) of 1.2 % while that in KEEA was on a relatively smaller scale AR of 23/100,000 but with a high case fatality rate of 18.8 %. For both districts, we identified multiple strengths in the response to the outbreak including timely notification of the district health officials which triggered prompt investigation of the suspected outbreak facilitating confirmation of cholera and initiation of public health response activities. Others were coordination of the activities by multi-sectoral committees, instituting water, sanitation and hygiene measures and appropriate case management at health facilities. We also found areas that needed improvement in both districts including incomplete surveillance data, sub-optimal community based surveillance considering the late reporting and the deaths in the community and the inadequate community knowledge about cholera preventive measures.

The assessment of the cholera outbreak response in the two districts highlighted strengths in the epidemic control activities. There was however need to strengthen preparedness especially in the area of improving community surveillance and awareness about cholera prevention and the importance of seeking prompt treatment in health facilities in the event of an outbreak.

Carrion’s disease is a neglected tropical disease caused by Bartonella bacilliformis, a vector-borne pathogen restricted to the Andean valleys of Peru, Ecuador and Colombia. Carrion’s disease is a biphasic illness; in the acute phase the case-fatality rate can be as high as 88 %, related to high parasitemia, arriving to almost all erythrocytes, and secondary bacterial infections close related with the development of transient immunosuppression in the earlier illness phases. In addition, there are an undefined number of asymptomatic carriers that are reservoirs of the etiological agent of Carrion’s disease in endemic areas, they make take into account due to they are the perpetuators of this disease. The actual scenario of Carrion’s disease, in which the illness is arriving to new areas, due to the expansion of the vector’s distribution, suggests that now may be a crucial time to design a strategy focusing on its elimination.

Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children. The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.

Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media, of whom 11 carry the A2ML1 duplication variant. Ear swabs were submitted for 16S rRNA gene sequencing.

Genotype-based differences in microbial richness, structure, and composition were identified, but were not statistically significant. Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes, and genus Fusobacterium were nominally increased in carriers compared to non-carriers, but were non-significant after correction for multiple testing. We also detected rare bacteria including Oligella that was reported only once in the middle ear.

These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome. Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.